THE EFFECT OF FGF-3 INT-2 ON GROWTH AND TRANSFORMATION OF MCF-10A NORMAL HUMAN MAMMARY EPITHELIAL-CELLS IS DISTINCT FROM FGF-1 AND FGF-2

Fibroblast growth factors (FGFs) are related polypeptides with mitogen ic activity on cells of mesodermal and neuroectodermal origin. The Fgf -3 gene shares high homology with FGF-2 and its protein product can su bstitute FGF-2 as a growth factor. Other observations, however, indica te that Fgf-3 has specialized functions. We have investigated the effe ct of the expression and secretion of Fgf-3 on the growth and transfor mation of the human breast epithelial cell line MCF-10A. Overexpressio n of Fgf-3 stimulates proliferation of these cells in serum-free mediu m and induces anchorage-independent colony formation in soft agar. In contrast, these effects were not observed with purified FGF-1 and FGF- 2 on either the parental or the Fgf-3-MCF-10A cells. Thus, Fgf-3 is di stinct from FGF-1 and FGF-2 for its ability to induce cell proliferati on and transformation of MCF-10A cells. This difference could be due, at least in part, to the expression of a specific set of FGF receptors with higher affinity for FGF-3 than FGF-1 or FGF-2.